Pazienti con Genotipo 1 e Cirrosi Scompensata, pre-/post-olt

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1 Monotematica AISF 2013 Pazienti con Genotipo 1 e Cirrosi Scompensata, pre-/post-olt Pietro Andreone Dipartimento di Scienze Mediche e Chirurgiche Alma Mater Studiorum, Università di Bologna Pisa, Ottobre 2013

2 Pietro Andreone Università di Bologna Il sottoscritto dichiara di aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione MSD Janssen Cilag Roche e che la presentazione non contiene discussione di farmaci in studio o ad uso off-label

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4 Prototypes Decompensated liver cirrhosis Compensated liver cirrhosis with HCC Post-OLT recurrence

5 Decompensated liver cirrhosis prototype EASL Guidelines In patients with Child Pugh B cirrhosis, antiviral therapy is offered on an individual basis in experienced centers, preferentially in patients with predictors of good response (C2). Norfloxacinprophylaxis should be given if ascites is present (C2). Patients with Child Pugh C cirrhosis should not be treated with the current antiviral regimen, due to a high risk of life-threatening complications (C1). J Hepatol 2011

6 Compensated liver cirrhosis with HCC prototype EASL Guidelines Antiviral therapy is indicated in patients with conserved liver function (Child Pugh A) in whom the indication for transplantation is HCC(B2). J Hepatol 2011

7 Compensated liver cirrhosis with HCC prototype History ofa case Male, 64 yrs, retired medical doctor BMI29; high HOMA-R; HCV(G1b) livercirrhosis unresponsive to 3 treatment courses (partial responder at the last on 2007) 2012 July: HCC 3.2 cm in S3; MELD 7; CTP 5 October: liver resection without decompensation November: listed for OLT December: start lead-in withpeg-ifn+rbv (PLT mm 3 ; Albumin3.8 g/dl) 2013 January: addeltrombopag for PLTpenia ( mm 3 ) February: after 9 week of lead-in (HCV-RNA <1 log decrease) start TVR 4 wkafter TVR: HCV-RNA negative 11 wk after TVR: rash grade 3 stop TVR, continues PEG+RBV May: liver transplantation October: no HCV recurrence

8 Compensated liver cirrhosis with HCC prototype History ofa case Male, 68 yrs, retired medical doctor BMI29; high HOMA-R; HCV(G1b) livercirrhosis unresponsive to 3 treatment courses (partial responder at the last on 2007) 2012 July: HCC 3.2 cm in S3; MELD 7; CTP 5 October: liver resection without decompensation, not listed for OLT for age you would have changed the indication to triple therapy?

9 Compensated liver cirrhosis with HCC prototype Are there variables affecting treatment indication? Naive/PR experienced? Host genetics? Baseline viral load?? Response to PR lead-in? Liver function? Yes: tolerability/rvr Yes

10 Post-OLT recurrence prototype AISF Guidelines 1. Triple therapy with BOC or TVRshould be considered for recurrent hepatitis C in liver transplant recipients, in case of at least moderate fibrosis ( F2) (B1) 2. Even in absence of available data, transplant recipients who develop a fibrosingcholestatichepatitis can be treated with triple therapy, due to therapeutic urgency (C1) DLD in press

11 Male, 58 yrs, public employee BMI 25; no diabetes; paroxysmal atrial fibrillation; patent foramen ovale HCV(G1b) livercirrhosis unresponsive to 2 treatment cycles (null responder) 2012 February: 2 HCC nodules treated withtace + PEI; decompensation October: cardiac surgery for patent foramen ovale December: listed for OLT (MELD 12; CTP B8) 2013 April: OLT May: severe HCV recurrence (bilirubin 12 mg/dl); start triple Tx with TVR June: HCV-RNA negative after 4 wks with a dramatic clinical improvement July: severe rash after 8 wks Post-OLT recurrence prototype History ofa case

12 Post-OLT recurrence prototype History ofa case Evolution from grade 1 to 3 in two days during CSA and steroids treatment! Switch from TVRto BOC

13 Post-OLT recurrence prototype Influence ofil28b (860 snp) on SVRresponse in LT Duarte-Rojo A et al, Liver Transplant 2013

14 Post-OLT recurrence prototype Howto optimize antiviral treatment Pungpapong S et al, Liver Transplant 2013

15 Hepato artist! Quadro istologico del fegato appartenuto alla mummia naturale GVSG 03. Marcata degenerazione cellulare con residue strutture fibrovascolari, con aspetti simili ad un ritratto espressionista (Ematossilina-eosina, ingrandimento iniziale: 40x).